There is no effective treatment for many congenital enzymatic deficiency diseases; many of those patients affected die at an early age or suffer greatly throughout life. Whole organ transplantation has previously been successful at enzyme replacement in some individuals with enzymatic deficiency disease. However, this procedure is associated with significantly morbidity and mortality. The first objective of the proposed research is to isolate viable hepatocytes and to demonstrate their ability to replace a missing enzyme when transplanted into animals wth congenital enzymatic deficiency diseases. Two models will be utilized: a) the Gunn rat, deficient in the liver enzyme uridine diphosphate glucoronyl transferase (similar to the defect in Criglar-Najjar syndrome in humans , and b) the acatalasemic mouse, deficient in catalase. In both models hepatocytes will be isolated from normal animals and embolized into the portal circulation of the enzyme deficient animals. The infused hepatocytes will lodge in the liver sinusoids. The ability of the hepatocellular transplants to replace the deficient enzyme will be determined in the transplanted animals. Many patients die of acute, potentially reversible liver failure. In animal models, heterotropic liver transplantation can sustain life until host liver recovers. Whole organ liver transplantation is impractical in humans. Hepatocellular transplantation into the portal vein would be a simple and rapid method of providing functioning hepatocytes in these severely ill patients. Administration of dimethylnitrosamine to dogs results in a model of acute potentially reversible liver failure. This model will be utilized to evaluate the capability of portal vein hepatocellular transplantation to provide sufficient hepatic function to allow host liver to recover. The dog will also provide a sensitive model to determine the effect that infusion of hepatocytes has on the portal circulation by direct measurement of portal pressure.